The purpose of this research is to develop a non-viral gene delivery systems for the treatment of emphysema in alpha-1-antitrypsin (AT) deficient patients. AT deficiency leads to protease-induced damage in the lung which can develop into emphysema. Currently there are no adequate means to inhibit disease progression. AT protein therapy has been shown to only temporarily ameliorate disease progression while viral gene delivery systems are under development this approach will be hampered by limitations of immunological reaction of the host. Non-viral gene therapy has the potential to circumvent many of the immunological and infectivity problems associated with viral gene therapy and provide for a more durable treatment than protein therapy for emphysema patients. We hypothesize that cationic liposome gene delivery systems can efficiently transfect lung epithelial cells. Improvement of nucleic acid delivery to lung tissue will allow adequate production of AT protein to levels sufficient to combat alveolar destruction and reverse or prevent disease. This research will provide insight into the parameters governing cationic liposome-mediated gene delivery, and computational approaches and computer graphics will permit a more rational design of subsequent generations of cationic liposomes for gene therapy.